Original Article

Sex Dev 2022;16:19–26 Received: March 24, 2021

Accepted: June 23, 2021
DOI: 10.1159/000518092 Published online: August 10, 2021

Can Boys Have Turner Syndrome?

More than a Question of Semantics
Michelle M. Knoll a Julie Strickland b Jill D. Jacobson a

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aDivision
of Endocrinology, Department of Pediatrics, Children’s Mercy Kansas City, Kansas City, MO, USA;
bDivision
of Gynecology, Department of Surgery, Children’s Mercy Kansas City, Kansas City, MO, USA

Keywords tine screening of boys following the Turner Syndrome Clini-

Differences of sex development · Short stature · Turner
syndrome
Abstract
Individuals with 45,X mosaicism with Y chromosome mate-
rial raised as boys are not diagnosed with Turner syndrome,
a label restricted to phenotypic females. We sought to deter-
mine if boys with 45,X mosaicism had features consistent
with Turner syndrome. Twenty-two patients (14 girls, 8 boys)
seen in our Differences of Sex Development (DSD) clinic
were identified for review. Standardized height (z-scores) by
sex of rearing and results of cardiology, renal, audiology, thy-
roid, and celiac screenings were recorded. All subjects had
heights below the mean for sex. Z-scores were not signifi-
cantly different between boys and girls (p = 0.185). There
were no significant differences in the incidence of cardiac
anomalies between boys and girls (p = 0.08). Girls were more
likely to have additional screenings (p = 0.042), but there
were no significant differences in the number of positive
screenings between boys and girls (p = 0.332). Patients with
45,X mosaicism raised as boys appear to have features simi-
lar to patients with the same karyotype raised as girls. Rou-
cal Practice Guidelines may allow early recognition of co-
morbidities. Additionally, obtaining karyotypes on boys with
short stature or other features of Turner syndrome may iden-
tify unrecognized cases of 45,X mosaicism.
© 2021 S. Karger AG, Basel
Introduction
Turner syndrome (TS) was described in 1930 [Wiede-
mann and Glatzl, 1991] and again in 1938 [Turner, 1938]
as a disorder affecting women that is characterized by
webbed necks, low hairlines, and minimal or absent pu-
bertal development. In 1959, the genetic basis of TS was
described as XO [Ford et al., 1959]. However, as the Y
chromosome was not identified until the 1960s [Griffiths,
2018], women with TS were initially thought to have the
same chromosomal makeup as typical men. Our under-
standing of the genetic basis of TS has evolved consider-
ably over the past several decades, and we now under-
stand the genotypic variability that presents as TS. It is
known that 10–12% of individuals with TS have
45,X/46,XY mosaicism [Gravholt et al., 2017]. However,

karger@karger.com © 2021 S. Karger AG, Basel Correspondence to:

www.karger.com/sxd Michelle M. Knoll, mmk6ac @ virginia.edu
phenotypic males with 45,X mosaicism are not consid-
ered to have TS, as the diagnosis requires that the indi-
vidual be phenotypically female [Gravholt et al., 2017].
Males with 45,X mosaicism are historically identified be-
cause of the presence of genital atypia. More recent data
suggest that the majority of individuals with this chromo-
somal pattern do not have genital atypia [Chang et al.,
1990], and many more are diagnosed as part of infertility
evaluations [Ljubicic et al., 2019].
Current guidelines for surveillance of girls with TS in-
clude serial cardiac evaluations, renal ultrasound at diag-
nosis, monitoring of growth and puberty, and evaluation
for gonadal tumors in those with Y chromosome mate-
rial. There is no definitive age for starting growth hor-
mone (GH) treatment, but evidence indicates younger
age at treatment initiation and longer duration of therapy
results in improved height outcomes [Gravholt et al.,
2017]. Several studies have investigated clinical outcomes
of boys with 45,X mosaicism, with respect to height, car-
diac anomalies, renal anomalies, gonadal tumor risk, fer-
tility and response to GH [Telvi et al., 1999; Richter-Un-
ruh et al., 2004; Tosson et al., 2010, 2012; Efthymiadou et
al., 2012; Lindhardt Johansen et al., 2012; Martinerie et
al., 2012; De Groote et al., 2013; Bertelloni et al., 2015;
Hojat and Schweiger, 2015; Wu et al., 2017; Dumeige et
al., 2018; Ljubicic et al., 2019]. Results suggest that this
population is at risk of features associated with TS. How-
ever, most of these studies focus on 1 or 2 of these fea-
tures, resulting in an incomplete clinical picture. No cur-
rent guidelines exist for following these children long-
term, though a review by Colindres et al. [2016] provides
some recommendations for monitoring gonadal function
and short stature throughout the lifespan.
We noted that several individuals with 45,X mosa-
icism with Y chromosome material raised as boys in our
multidisciplinary Difference of Sex Development (DSD)
clinic carried several features of TS including short stat-
ure and cardiac anomalies. We sought to determine
whether these boys displayed similar rates of comorbidi-
ties compared to girls with 45,X mosaicism with Y chro-
mosome material. We also sought to determine whether
they were screened and treated according to the TS guide-
lines.
Materials and Methods
This study is a retrospective review of patients seen in Chil-
dren’s Mercy’s multidisciplinary DSD clinic between April 2008
and October 2020. Patients were referred to the clinic if they had
genital atypia, discrepancy between phenotype and sex chromo-
20 Sex Dev 2022;16:19–26
DOI: 10.1159/000518092
12
Sex of rearing
■ Female
10 ■ Male
8
Frequency
6
4
*
2
0
0 2 4 6 8 10 12
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External masculinization score
Fig. 1. External masculinization scores by sex of rearing. Asterisk
denotes girl with comorbid congenital adrenal hyperplasia.
some genotype, sex chromosome mosaicism, or TS with Y chro-
mosome mosaicism. A total of 222 patients were seen during this
time. The subset of patients with a 45,X cell line on chromosomal
analysis (n = 22) is the focus of this analysis. Fourteen patients were
raised as girls and 8 were raised as boys.
Medical records were reviewed for clinical information includ-
ing ages at clinic visits. Sex of rearing was documented for each
patient. In cases of genital atypia, sex of rearing was determined
based on evidence of prenatal androgen exposure, evidence of go-
nadal function (including location of gonads), hormone levels, and
discussion with the family. Genital phenotype was characterized
based on records of clinical exams and scored using the External
Masculinization Score (EMS) [Ahmed et al., 2000]; a phenotypi-
cally typical girl has an EMS of 1 (0.5 points for each intra-abdom-
inal gonad), whereas a phenotypically typical boy has an EMS of 12.
Pathology reports from any gonadal surgery (e.g., gonadectomy or
gonadal biopsy) were reviewed for evidence of malignancy. Linear
growth measurements were recorded as the most recent height and
z-score prior to initiation of growth hormone treatment, if pre-
scribed. Mid-parental height (MPH) was also obtained by parent
report. MPH was converted to z-score based on data from Centers
for Disease Control and Prevention growth charts, using a mean
adult height for men of 176.8 cm (SD 7.1 cm) and a mean adult
height for women of 163.3 cm (SD 6.4 cm) [Centers for Disease
Control, 2019]. Height z-scores were then corrected for MPH by
subtracting height z-score from MPH z-score. One girl also had
21-hydroxylase deficiency and was excluded from height analysis
to avoid confounding effect but was included in other analyses.
Screening for additional comorbidities was assessed according
to the TS consensus guidelines [Gravholt et al., 2017] and included
cardiology evaluation (imaging and electrocardiogram), renal
evaluation, audiology testing, and thyroid function, which are rec-
ommended at the time of diagnosis. Additional screenings includ-
ed celiac disease for patients older than age 2 years, and Hemoglo-
bin A1c, liver function tests, and 25-OH Vitamin D level for pa-
tients older than 10 years. For each patient, these screens were
scored as not done, normal, or abnormal.
Knoll/Strickland/Jacobson
 0 0
–1
Height z-score
–2
–3
–4
Female Male
Sex of rearing
Fig. 2. Height z-score for each subject.
Patients were divided into groups based on sex of rearing. Con-
tinuous variables were analyzed using Mann-Whitney U, and cat-
egorical variables were analyzed using χ2 or Fisher’s exact Test.
This study was approved by the institutional review board at Chil-
dren’s Mercy Kansas City. A waiver of informed consent was
granted due to the retrospective nature of the analysis.
Results
EMS was significantly lower in patients raised as girls
(median 1.0, 1.0–7.0) compared to those raised as boys
(median 8.25, 6.0–12.0), U(22) = 110, z = 4.026,
p < 0.001 (Fig. 1). Boys had significantly more genital
atypia than did girls, as determined by Delta EMS (the
absolute value of EMS – expected EMS based on sex of
rearing; U(22) = 97, z = 3.143, p = 0.004). Only 2 girls
demonstrated genital atypia, compared to 7 of the boys.
Bilateral gonadectomy was performed in all girls, which
demonstrated germ cell tumors in 7/28 gonads. Gonad-
ectomy and gonadal biopsies were not routinely per-
formed in boys, although 4 had unilateral gonadectomies
that showed no histologic evidence of neoplasm.
All patients had heights less than the mean for the sex
of rearing. Height z-scores prior to initiation of growth
hormone treatment were not significantly different be-
tween boys (median −2.57, −3.78 to −0.59) and girls (me-
dian −1.7, −3.20 to −0.54), U(21) = 33, z = −1.376, p =
0.185 (Fig. 2). Three patients (1 girl, 2 boys) did not have
MPH available for analysis. When height z-scores were
corrected for MPH, there were also no significant differ-
Sex Differences in 45,X/46,XY Mosaicism
–1
Delta z-score
–2
–3
–4
Female Male
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Sex of rearing
Fig. 3. Delta height z-score (MPH z-score minus height z-score)
for each subject.
ences between boys (median −2.11, −3.65 to −1.64) and
girls (median −2.74, −3.37 to −0.42), U(18) = 40, z =
0.375, p = 0.750 (Fig. 3). There were insufficient data to
generalize about final adult heights, as most patients were
still growing at the time of their most recent clinic visits.
Growth hormone use is denoted in Table 1. Notably, 2
boys were treated with growth hormone early (started be-
fore 4 years of age) and had height SD within the normal
range for age (−0.06 and −0.47, mean −0.26) at their last
clinic visit.
There were insufficient numbers of screens done in
each group to perform analysis on individual screening
tests, other than cardiac screening. Results of screening
evaluations are presented in Table 1. Non-cardiac
screenings were inconsistently performed in both
groups. Girls were significantly more likely than boys
to have screenings completed (performed/eligible:
92/102 vs. 37/58, χ2(1) = 16.501, p < 0.001). However,
the number of abnormal screens did not differ signifi-
cantly between boys (6/37, 16%) and girls (10/92, 11%),
p = 0.405. The types of renal anomalies were similar be-
tween the 2 groups.
All patients had cardiology evaluations. The most
common anomaly was bicuspid aortic valve (8/22), fol-
lowed by aortic anomalies (5/22). The males often had
other cardiac anomalies, including atrial septal defect, hy-
poplastic left heart syndrome, and dilated coronary sinus.
There were no significant differences in the incidence of
cardiac anomalies between boys (5/8, 62.5%) and girls
(11/14, 78.6%), p = 0.369.
Sex Dev 2022;16:19–26 21
DOI: 10.1159/000518092
 22
Table 1. Clinical characteristics of children with 45,X mosaicism with Y chromosome material

Subject Reason for Age, Sex EMS Ht SD GH Karyotype (tissue) Cardiac Renal
referral yearsa treatmentb

1 Genital atypia 0.02 F 2.5 −1.97 Early 45,X[92]/46,X,idic(Y)(q11.2)[8] (fibroblasts) + –

BAV
2 Genital atypia 0.75 F 7.0 n/ac None 45,X[40]/45,X,tas(Y;16)(p11.32;p13.3)[40]/45,X,tas(Y;8) + –
(p11.32;p23.2)[20] (blood) Small PFO
3 Short stature 14.75 F 1.0 −2.16 None 45,X[20]/46,XY[55]/47,XYY[25] (blood) + +
Pseudocoarctation, borderline Absent right kidney
prolonged QTc
4 Short stature 5.92 F 1.0 −3.20 Late 45,X[40]/45,X,idic(Y)(p11.32)[60] (blood) + –
BAV

Sex Dev 2022;16:19–26

DOI: 10.1159/000518092
5 Prenatal Dx 0.25 F 1.0 −0.54 Early 45,X[65]/46,XY[35] (gonadal tissue) + –
Coarctation, BAV
Aortic root dilation
6 Prenatal Dx 0.42 F 1.0 −2.72 Early 45,X[30]/46,XY[70] (blood) + –
BAV, dilation of ascending aorta
7 TS Stigmata 0.50 F 1.0 −2.16 None 45,X[65]/46,X,idic(Y)[35] (blood) – +
Dysplastic left
kidney
8 Autismd 4.25 F 1.0 −0.78 None 45,X[35]/46,X,idic(Y)[65] (blood) + +
BAV Duplex right kidney
9 Prenatal Dx 0.42 F 1.0 −1.58 None 45,X[55]/46,X,idic(Y)[35]/47,X,idic(Y),idic(Y)[10] (blood) + +
Mild coarctation Cyst of left kidney
10 Cardiac 0.92 F 1.0 −2.82 Early 45,X[70]/46,XY[30] (blood) + –
anomaliesd Small PDA, BAV, aortic root dilation
11 Short stature 12.16 F 1.0 −1.48 Late 45,X[30]/46,XY[70] (blood) + –
BAV, trivial aortic stenosis
12 Lung Diseased 4.42 F 1.0 −1.56 Late 45,X[50]/46,X,idic(Y)[50] (blood) + –
PDA, aortic root dilation
13 Short stature 9.33 F 1.0 −1.54 Late 45,X[40]/46,XY[60] (blood) + –
BAV, mild aortic regurgitation
14 Short stature & 15.58 F 1.0 −1.70 Late 45,X[40]/46,XY[60] (blood) – +
Delayed Duplex L kidney
puberty

Knoll/Strickland/Jacobson
15 Short stature 9.25 M 10.5 −0.92 None 45,X[40]/46,X,idic(Y)(q11.23)[30]/46,XY [30] (gonadal – n/a
tissue)
16 Genital atypia 2.0 M 8.0 −2.19 Early 45,X[42]/46,X,idic(Y)(q11.23)[47]/46,X,idic r(Y)[11] (blood) – –

17 Prenatal Dx 0.16 M 6.5 0.23 None 45,X[80]/47,XXY[20] (blood) + –

PFO

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 Discussion

≥4 years old at start. c Subject excluded from height analysis due to diagnosis of congenital adrenal hyperplasia. d Subjects underwent genetic testing for consideration of condition noted and were
BAV, bicuspid aortic valve; PFO, patent foramen ovale; PDA, patent ductus arteriosus; ASD, atrial septal defect. a Age at first evaluation. b Early defined as <4 years old at start, late defined as
Horseshoe kidney
collecting system
Duplex left renal
This study adds to a growing body of literature inves-
tigating the long-term effects of 45,X mosaicism on indi-
viduals raised as boys. The 2016 Clinical Practice Guide-
Renal

n/a
line for TS specifically state that “Turner syndrome is a
+

+
–

–
PFO, dilated coronary sinus, persistent
chromosomal disorder that affects phenotypic females
who have one intact X chromosome and a complete or
partial absence of the second sex chromosome in asso-
ciation with one or more clinical manifestations” (em-
left superior vena cava phasis original) [Gravholt et al., 2017]. Given that 10–
Hypoplastic left heart

12% of girls with TS have Y chromosome components,

Moderate ASD

this distinction seems to be arbitrary and based on his-

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toric norms rather than on scientific rationale. Tosson et
Tiny PFO
Cardiac

al. [2012] argued that 45,X/46,XY mosaicism should be

considered a separate entity from TS with its own man-
+

agement guidelines. However, after comparing the 16

patients in their cohort, they concluded that all these
children should undergo evaluation similar to that per-
formed in TS, in addition to any necessary urological
studies based on their anatomy. It should be noted that
the guidelines already account for some of these differ-
45,X[80]/46,X,idic(Y)[20] (gonadal tissue)

45,X[51]/46,X,idic(Y)(p11.3)[49] (blood)

ences, as it is recommended that girls with Y chromo-

some material undergo further evaluation because of the
45,X[75]/46,X,idic(Y)[25] (blood)
45,X[7]/46,X,idic(Y)[93] (blood)

risk of gonadal tumors.

45,X[60]/46,XY[40] (blood)

Many of the subjects in our study had differences in

genital phenotype, but this finding likely represents a re-
ferral bias given that our population was seen in a DSD
Karyotype (tissue)

clinic. A study examining prenatally diagnosed cases of

45,X/46,XY mosaicism found that the majority of pa-
tients did not have genital atypia [Chang et al., 1990], sug-
gesting underdiagnosis of this condition. For those boys
referred to our clinic as infants, discussion regarding sex
treatmentb

of rearing focused on whether there was evidence of func-

None

None

None
Early

Early

tional testicular tissue, as indicated by degree of mascu-

GH

linization, location of the gonads, and hormonal testing,

as well as values of the family. All boys had an EMS of 6.0
EMS Ht SD

−1.91

−3.61

−1.68

−2.76

−1.85

or greater. Only one infant reared as female had an EMS

>6; she had a co-morbid diagnosis of 21-hydroxylase de-
12.0
7.5

8.5

8.5

6.0

ficiency which was felt to be the cause of her virilized gen-

italia. It is unclear why similar karyotypes result in differ-
Sex

ent genital phenotypes as seen in our subjects. Previous

yearsa

analyses have suggested that the proportion of Y chromo-

Age,

found to have a 45,X cell line.

Genital atypia 0.75

Genital atypia 6.84

0.02

Genital atypia 0.75

Genital atypia 0.25

some material in the gonadal cell lines influences the gen-

ital phenotype [Guedes et al., 2006], though others have
Table 1 (continued)

Prenatal Dx
Subject Reason for

suggested additional complexity in gonadal development

referral

in these patients [Shinawi et al., 2010]. Those boys re-

ferred to our DSD clinic for reasons other than genital
atypia (e.g., short stature or prenatal testing) tended to
have less genital atypia.
18

19

20

21

22

Sex Differences in 45,X/46,XY Mosaicism Sex Dev 2022;16:19–26 23

DOI: 10.1159/000518092
 Growth failure and reduced adult height are consid-
ered the most common manifestations of TS, leading to
the recommendation that a karyotype should be obtained
in any girl with unexplained growth failure with or with-
out other features of TS [Gravholt et al., 2017]. Any pa-
tient with 45,X/46,XY being raised as a girl is considered
an automatic candidate for growth hormone therapy, re-
gardless of her GH testing results. Our study demon-
strates that patients with 45,X mosaicism raised as boys
have similar degrees of short stature compared to those
raised as girls, extending the findings of other studies
[Telvi et al., 1999; Richter-Unruh et al., 2004; Tosson et
al., 2010; Lindhardt Johansen et al., 2012; Martinerie et
al., 2012; Bertelloni et al., 2015; Colindres et al., 2016; Du-
meige et al., 2018; Ljubicic et al., 2019]. Given that there
is no consensus recommendation on obtaining karyo-
types in boys with short stature, 45,X mosaicism in boys
is likely underdiagnosed in childhood and the associated
growth failure in this population goes untreated. Current
data also suggest boys with 45,X mosaicism do not have
robust responses to treatment with growth hormone. In
a review of GH use in boys with 45,X/46,XY mosaicism,
the major limitations were small numbers of patients,
older age at initiation of treatment (mean age 10.9 years),
and shorter duration of therapy [Bertelloni et al., 2015].
A multicenter registry for boys with sex chromosome
mosaicism may aid in evaluating the growth of these pa-
tients with and without growth hormone treatment.
There is a paucity of data regarding other comorbidi-
ties seen in boys with 45,X mosaicism. Renal anomalies
are reported in some studies [Martinerie et al., 2012; Du-
meige et al., 2018], but not in all, so the exact prevalence
of these anomalies is unclear. One recent report describes
the prevalence of celiac disease in a group of patients with
monosomy X with Y chromosome material; all affected
patients were either raised as male or had genital atypia
[Guzewicz et al., 2021]. None of the available literature
reports on the prevalence of abnormal hearing screens.
One case series found 2 boys with hypothyroidism who
were ultimately diagnosed with 45,X/46,XY mosaicism in
the workup for short stature [Hojat and Schweiger, 2015].
With so few cases reported in the literature, it is challeng-
ing to know what the true risk of these comorbidities is,
again highlighting the importance of a multicenter regis-
try for this rare condition.
Females with 45,X/46,XY mosaicism are at risk of go-
nadal tumors, and some data are available about gonadal
tumor risk in males [Martinerie et al., 2012; Cools et al.,
2011; Matsumoto et al., 2020], though risk factors are not
clear in these studies. We did not assess gonadal tumor
24 Sex Dev 2022;16:19–26
DOI: 10.1159/000518092
risk in our cohort, as our male patients did not routinely
have gonadal biopsies or gonadectomies to determine
this risk and thus the comparison was underpowered.
However, gross pathology was normal in the 4 boys who
underwent unilateral gonadectomies. Many men are di-
agnosed with 45,X/46,XY mosaicism as part of infertility
evaluations, but many of those diagnosed seem to have
normal testosterone production and progress at least par-
tially through puberty [Layman et al., 2009]. The severity
of gonadal dysfunction in men is unclear, particularly in
comparison to the ovarian failure seen in women with TS.
This question warrants additional study.
Fewer studies have investigated whether boys have as-
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sociated cardiac anomalies, but data suggest the associa-
tion remains present in boys [Efthymiadou et al., 2012;
De Groote et al., 2013; Dumeige et al., 2018; Silvestre et
al., 2019]. Our subjects all had cardiac screening; boys and
girls showed no difference in the prevalence of cardiac
abnormalities. It is estimated that 1% of live births have a
cardiac defect, though this number specifically excludes
those with bicuspid aortic valve and other “minor” de-
fects [van der Linde et al., 2011], suggesting that cardiac
defects are more common in boys with 45,X mosaicism
than in the general population. However, boys with nor-
mal initial evaluations were likely to be discharged from
the cardiology clinic rather than having ongoing surveil-
lance as is recommended for girls with TS. Thus, in the
absence of recommendations, boys with 45,X mosaicism
are less likely to have this screening performed and may
be at a higher risk of cardiovascular morbidity and mor-
tality due to unrecognized disease.
Overall, these data point to a need for further studies
to determine the overall prevalence of 45,X mosaicism in
the general population. Earlier diagnosis of individuals
may allow for earlier recognition of these potentially seri-
ous comorbidities.
Our analysis is limited because of the small number of
patients. Additional descriptive information was also
limited by the retrospective nature of our chart review.
This was particularly noted with inconsistent documen-
tation about outside evaluations, such as ophthalmologic
exams and school performance, which are also recom-
mended as part of the TS screening guidelines [Gravholt
et al., 2017]. As some procedures are not routinely per-
formed in our clinic, the utility of our analysis (particu-
larly related to gonadal function in boys) may be limited.
In addition, our cohort is still very young, with only 4/8
male patients older than age 10 at the most recent visit
and only 1 patient has completed puberty. Therefore, we
are limited in our ability to assess factors such as pubertal
Knoll/Strickland/Jacobson
progression, fertility, and adult height in this group of
boys. Our study also differs from another recent study, as
we chose to categorize our cohort by sex of rearing, rath-
er than comparing girls to those with atypical genitalia
and boys [Guzewicz et al., 2021]. These sex of rearing de-
terminations were heavily influenced by appearance of
the genitalia as previously discussed.
The lack of screening in our male cohort is to be expect-
ed given that these individuals are not considered to have
TS, but we also found that some of our female cohort did
not have screenings done. Data from our institution suggest
that girls cared for outside of a multidisciplinary clinic are
less likely to have all recommended screenings performed
Statement of Ethics
This study is a subanalysis of a larger study approved by the
Institutional Review Board of Children’s Mercy Kansas City (study
15080356). Given the retrospective nature of the study, a waiver of
informed consent was granted.
Conflict of Interest Statement
The authors have no conflicts of interest to declare.
Funding Sources
This study did not have any extramural funding.

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[Hoag, unpubl. data]. This observation highlights the im-
portance of caring for all these patients in a multidisci-
plinary setting with experience in these conditions.
Although our study is small and cannot provide con-
clusive data, our findings suggest the benefit of a multi-
center registry to follow these children long-term. We
recommend that boys with 45,X mosaicism be monitored
for growth, cardiac anomalies, renal anomalies, and pu-
bertal progression, though there is likely benefit to screen-
ing all conditions associated with TS.
Acknowledgement
We thank the Medical Writing Center at Children’s Mercy
Kansas City for editing this manuscript.
Author Contributions
M.M.K. designed the study, collected all data, performed initial
statistical analysis, and drafted the manuscript. J.S. contributed to
the design of the study and critically revised the manuscript for
important intellectual content. J.D.J. contributed to the design of
the study, verified statistical analysis, critically revised the manu-
script for important intellectual content, and provided mentorship
throughout the research process.
Data Availability Statement
The data that support the findings of this study are not pub-
licly available due to information that could compromise the pri-
vacy of research participants given the rarity of the diagnosis in-
vestigated in this study. Data are available from M.K. upon reason-
able request.

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